The radioprotective compound, S-2-(3-aminopropylamino) ethylphosphorothioate (WR-2721) has shown the ability to selectively protect normal tissues in animals, leaving malignant tissues unprotected. Differential tissue concentration appears to be the mechanism for this therapeutic ratio. In the present study, several tumor-bearing animal strains have been analyzed for radiolabeled drug uptake. All show low concentration in tumor tissue, and high concentration in liver, kidney, gastrointestinal tract and salivary gland. Radiomicrosphere entrapment studies show greater flow in irradiated limbs of animals treated with WR-2721 prior to irradiation than in non-drug-treated animals, indicating protection of vasculoconnective tissues. Continuing studies are designed to further quantitate the radioprotection in liver, salivary gland and vasculoconnective tissues and in the tumor tissues showing low drug concentration. Acute and chronic normal tissue responses will be evaluated by radionuclide scanning technics, tissue enzyme levels, vascular radiomicrosphere entrapment and microscopy. Tumor response to the drug and irradiation will be analyzed by colony formation in tissue culture following in vivo treatment of tumor bearing animals. The clinical usefulness of WR-2721 becomes apparent as new data continue to indicate poor tumor-drug concentration in a variety of animal tumors, and radioprotection of normal tissue.